The proposed studies involve the identification of humoral factors important in the regulation of cellular hypersensitivity. We have adapted the desensitization model from guinea pigs to mice. By transferring a donor population of sensitized cells to a recipient animal, desensitization with donor antigen can be studied after manipulation of the transferred cell population. We propose to identify the subset of T cells responsible for desensitization in the recipient by the use of selective specific antiserum cytolysis. With this system in mice the limitations of strain specificity with respect to H-2 and Ia antigens will also be studied. Sensitized cells exposed to antigen in vitro have produced a desensitizing factor in supernates which will be studied as to enzyme lability, pH temperature and storage, stability. The factor will be characterized as to size and the cell of its production identified. Furthermore, the requirement for soluble antigen for the production of this factor as well as its identity or lack of it with known lymphokines such as MIF, LIF, MAF, CF and BF will be determined. In the guinea pig the desensitization system will be used to study whether the regulatory cell is a T cell and whether subsets of regulatory T cells are required for desensitization. Markers will be used to identify the subsets and functionally cyclophosphamide treatment will be employed to manipulate the subset of cells required for the desensitization reaction. The question of the relationship between classic delayed type hypersensitivity and cutaneous basophil hypersensitivity will be studied to determine how serum factors in DTH sensitized animals suppress CBH. The capacity of desensitized guinea pigs to accept a transfer of serum and/or cells known to be capable of transferring CBH will be investigated. Finally, the role of mediators, such as histamine and prostaglandin in influencing the desensitization reaction will be studied to address the question of the influence of Type-I mediators on Type-IV reactions and the desensitization phenomena.